Support, especially the functionalized support with selective reactivity has been applied extensively in many fields, especially in the fields of qualitative and/or quantitative analysis, or/and separation of targets in a sample. Affinity chromatography gel is an example of functionalized support whereas the antigen or/and antibody analysis-chip is an example of analysis application.
Most of present functionalized supports are produced by directly immobilizing functional reagent (e.g. probe-ligand) onto the surface of a support. For example, glass derivatives (such as amino-group glass slide, aldehyde-group glass slide, epoxy-group glass slide, polyamino acid-coated glass slide, etc.) are the main substrates used nowadays for analysis-chips. The immobilized functional reagent, produced by immobilizing the functional reagent onto the substrate, is one of the key factors deciding the test sensitivity and specificity of the analysis-chip. The available immobilization measures are mainly covalent bond immobilization, physicochemical adsorption, embedding, and cross-linking. The reaction kinetic condition for functional reagents is to be optimized and detailed, which is manifested as improved sensitivity or/and specificity; or/and to shortened reaction time.
How to improve the immobilized functional reagent through modifying the surface of a support has long been a major problem in R&D for analysis or/and separation, and has attracted many laboratories worldwide. Though many researchers are working on the modification of the support surface by using nano-particles or colloid, they either fail to take the sensitivity as the primary goal (e.g. WO 0183825), or fail to take the immobilized functional reagents as the main goal (e.g. USA Patent Application No. 20030207296), or obtain the support at an extremely high cost (e.g. the aligned nano-structured support by USA 3M Company, U.S. Pat. No. 5,709,943). In the document of WO 0183825, colloid, especially the organic particles at size of 100-500 nm is used, so as to decrease the workload in analysis-chip manufacturing, e.g. the processing procedures are so simplified as to produce analysis-chips with uniform probe spots. In the USA Patent Application No. 20030207296, the emphasis is laid on taking the nano-particle itself as the ligand support in the nucleic acid test. However the research on the modified nano-particle substrate is inadequate.
Another key factor for sensitivity and test time is the marking system. The prevalent marking system today is a molecular dispersion marking system whose sensitivity is yet to be improved, in which many labs are engaged. Some application of nano-particles has been introduced into the present marking systems in order to increase test sensitivity (such as WO 00/72018 A1, U.S. Patent Application No. 20030211488, whose research thereof uses colloidal gold as the labeling reagent, supplemented with silver enhancement system), but these particles are either labeling materials themselves, or reinforcing agents (e.g. U.S. Patent Application No. 20030232388, 20030166207, 20020142480, 20030211488, whose research thereof uses metals with raman enhancement effect). There are some patents wherein some nanometer crystal particles are employed as identifying codes of nano-particle supports, which connect molecules with varied activities (e.g. U.S. Pat. No. 6,544,732).
In addition, functionalized support is used extensively in separating device such as chromatography device, e.g., that comprising affinity chromatography gel. Although the particle employed by the functional matrix of chromatography has larger surface region than substrate, it leaves much to be desired in terms of chromatography time, and rate etc.